IMMUNOSUPPRESSION THERAPY Flashcards
(57 cards)
1
Q
What are
immunosuppressants?
A
- They are a group of drugs which are used to suppress rejection in organ transplants and are used to treat chronic inflammatory and autoimmune disease
- They can also be used in conditions such as inflammatory bowel disease
2
Q
Examples of immunisuppressants
A
- Anti-proliferative drugs
- Azathioprine
- Mercaptopurine
- Mycophenolate mofetil - Calcineurin inhibitors
- Ciclosporin
- Tacrolimus - Corticosteroids
- Prednisolone
3
Q
Azathioprine MOA
A
- Antimetabolite which breaks down into mercaptopurine
- inhibits the repairment and making of DNA
4
Q
Azathioprine - indications
A
- Prevents organ rejection in transplant patients
- Autoimmune disorders e.g. IBD, Rheumatoid arthritis, Myasthenia gravis
- May also be used for severe eczema
5
Q
Azathioprine - side effects
A
- Hypersensitivity → malaise, dizziness, D + V, fever, rash, hypotension, myalgia
- Bone marrow suppression (Neutropenia and thrombocytopenia) → report sore throat, bruising, bleeding
- Nausea → more common at start of dose but resolves over time
- Pancreatitis
- Teratogenic → avoid in pregnancy
6
Q
Azathioprine - hypersensitivity
A
malaise, dizziness, D + V, fever, rash, hypotension, myalgia
7
Q
Azathioprine - Neutropenia and thrombocytopenia
A
report sore throat, bruising, bleeding
8
Q
Azathioprine - nausea
A
- more common at start of dose but resolves over time
- divided doses, taken with food ro an antiemetic or reducing dose may help
9
Q
Azathioprine - monitoring requirements
A
- Thiopurine Methyltransferase (TPMT)
- Regular LFT and FBC in severe liver / renal impairment
- FBC weekly for first 4 weeks, then at least every 3 months
10
Q
Azathioprine - caution
A
- Reduced Thiopurine methyltransferase (TPMT)
activity
11
Q
Azathioprine - TMPT levels
A
- Azathioprine broken down by Thiopurine Methyltranaterase (TPMT)
- Reduced TMPT → risk of bone marrow suppresssion (myelosuppression), due to lack of metabolism
12
Q
Azathioprine - interactions
A
Allopurinol
ACEi
13
Q
Azathioprine + Allopurinol →
A
- increased risk of haematological toxicity
- Reduce dose of azathioprine to a quarter of the usual dose
14
Q
Azathioprine + ACE-I →
A
increased risk of anaemia / leucopenia
15
Q
Azathioprine - pregnancy
A
- NEVER
- The need to continue Azathioprine during pregnancy should be discussed with a specialist
- Pre-mature birth and spontaneous abortion have been reported
- Present in low levels in breastmilk
16
Q
Which is both an immunosuppressant and a cytotoxic drug?
Azathioprine or
Mercaptopurine?
A
- Mercaptopurine
- Azathioprine is only an immunosuppressant drug, it is not used as an anti-cancer (cytotoxic) drug
17
Q
Mercaptopurine - indications
A
- Severe Acute ulcerative colitis and Crohn’s (however use of it is unlicensed)
- Maintenance of remission of UC and Crohn’s
- Leukaemia
18
Q
Ciclosporin - MOA
A
Calcineurin inhibitor inhibiting lymphokines → suppress cell-mediated response
19
Q
Ciclosporin - indications
A
- IBD
- Rheumatoid arthritis
- Severe atopic dermatitis and psoriasis
- Organ transplantation
- Bone-marrow transplantation
20
Q
Ciclosporin - CI
A
- Uncontrolled hypertension!
- Malignancy
- Uncontrolled infections
21
Q
Ciclosporin - brand
A
Prescribed and dispensed by brand name
22
Q
Ciclosporin - pregancy + BF
A
Avoid
23
Q
Ciclosporin - side effects
A
HYPER- glycaemia, lipidaemia, tension, uricemia, kalaemia (HYPO-Mg)
Renal / Liver impairment
Skin reactions
Gingival hyperplasia
Hair changes
Eye inflammation and visual disturbances (in topical use with eyes)
24
Q
Ciclosporin - Interactions
A
- Grapefruit + Pomelo juice → increases ciclosporin exposure
- Purple grape juice → decreases ciclosporin exposure
- Macrolides
- Carbamazepine
- Amiodarone/ digoxin
- Statins
- Phenytoin
- Rifampicin
- Grapefruit juice
- Antifungals
- Tacrolimus
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Grapefruit + Pomelo juice →
| Ciclosporin
increases ciclosporin exposure
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Ciclosporin + Purple grape juice →
decreases ciclosporin exposure
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Ciclosporin - pre-screening
Pre-screening: exclude malignancies before systemic use
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Ciclosporin - monitoring
* Monitor: LFT, Magnesium, Potassium, Lipids, CrCl, Blood Pressure, Renal
* Trough levels need to be monitored (range depends on indication)
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Ciclosporin - counselling
* Avoid exposure to UV light / sunlight
* Topical (eye) use may effect driving / performing skilled tasks
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Tacrolimus - MOA
Calcineurin inhibitor inhibiting lymphokines → suppress cell-mediated response
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Tacrolimus - brands
1. Increased risk of infections
2. Neurotoxicity
3. QT prolongation
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Tacrolimus - brand
Prescribed and dispensed by brand name
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Tacrolimus - side effects
HYPER- glycaemia, uricemia, kalaemia
HYPO/HYPER tension
Renal / Liver impairment
Skin reactions
Visual disturbances
Blood Dyscrasia
Cardiovascular diseases (QT prolongation, cardiomyopathy in children)
Nervous system disorder, peripheral neuropathy
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Tacrolimus - pregnancy + bf
Avoid in pregnancy and breast feeding
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Tacrolimus - interactions
Grapefruit + Pomegranate + Pomelo juice → increases tacrolimus exposure
36
Grapefruit + Pomegranate + Pomelo juice →
increases tacrolimus exposure
37
Tacrolimus - contraindications
Do not use if patient has hypersensitivity to macrolides
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Tacrolimus - monitoring
1. Tacrolimus-blood concentration
2. BP
3. ECG - for risk of cardiomyopathy
4. Fasting-blood glucose concentration
5. Electrolytes
6. Renal function / Hepatic function
7. Vision
39
Tacrolimus - counselling
Avoid exposure to UV light / sunlight
May effect driving / performing skilled tasks
40
Mycophenolate Mofetil - indication
- Prevents rejection in: renal, cardiac and hepatic transplant
41
Mycophenolate Mofetil - MOA
* Inhibits purine synthesis
* Metabolised to mycophenolic acid
42
Mycophenolate vs Azathioprine
- Mycophenolic acid has a more selective mode of action that mercaptopurine
- Therefore it is more specific in preventing acute rejection
- Risk of blood disorders higher with myco
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Mycophenolate Mofetil - cautions
- GI disease
- Children/elderly
- Increased susceptibility to skin cancer
- hypogammaglobulin or bronchiestasis
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Mycophenolate Mofetil - side effects
Bone marrow suppression:
Pure red cell aplasia:
Hypogammaglobulinaemia:
Bronchiectasis
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Mycophenolate Mofetil - Bone marrow suppression
report infection or bruising or bleeding
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Mycophenolate Mofetil - pure red cell aplasia
reduce dose or discontinue
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Mycophenolate Mofetil - Hypogammaglobulinaemia
measure immunoglobulin levels in recurrent infections
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Mycophenolate Mofetil - bronchiectasis
Consider if persistent cough and SOB develops
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Mycophenolate - pregnancy
- PPP
- congenital malformations
- spontaneous abortions
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Mycophenolate Mofetil - MHRA Contraception Advice (teratogenic):
* Women: 1 effective contraception during and 6 weeks after (2 methods preferred)
* Men: effective contraception during and 90 days after (for partner as well)
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Mycophenolate - monitoring
FBC
- every week for 4 weeks
- twice a month for 2 months
- then every month
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What are the indications for
Corticosteroids as an immunosuppressant?
- They are used in IBD
- Corticosteroids are also used in transplant rejection
- Prednisolone also has an anti-tumour effect, therefore used in oncology
53
Summary
1. Azathioprine
- Metabolised to Mercaptopurine
- Do NOT use if TPMT low
- Bone marrow suppression is the main side effect
2. Mercaptopurine
- Do NOT use if TPMT low
- Immunosuppresant and cytotoxic
- higher risk of incorrect dosing
3. Mycopnenolate moreti
- Bone marrow suppression is the main side effect
- The key thing to remember is contraception advice is for both MEN and WOMEN
4. Ciclosporin
- Should always be prescribed by brand!
- Monitor: BP, lipids, Electrolytes (K and Mg), Renal and liver
5. Tacrolimus
- Should always be prescribed by brand!
- The same monitoring as Ciclosporin applies, but monitor blood glucose, ECG and Neurotoxicity for Tacrolimus
- Risk of Neurotoxicity, Hyperglycaemia, and cardiomyopathy are greater with Tacrolimus than with ciclosporin
54
What vaccines would p atients on immunosup pressants require?
1. Measles
- Advise to avoid anyone with measles
2. Varicella-Zoster (Chickenpox)
- Advise to avoid contact with chicken pox
55
Which vaccines should be AVOIDED for patients on
immunosuppressants?
LIVE VACCINES
- Patients can get the actual infection from the vaccine
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